Comparison of the stability and pharmacokinetics in dogs of modified ciclosporin capsules stored at −20°C and room temperature

Background Placement of ciclosporin (Atopica®; Novartis Animal Health, Greensboro, NC, USA) capsules in a freezer prior to administration may reduce the incidence of vomiting in dogs. However, its impact on ciclosporin stability and pharmacokinetics is unknown. Hypothesis/Objectives The purpose of this study was to evaluate the stability of Atopica® capsules and pharmacokinetics of ciclosporin in dogs after storage at −20°C in comparison with storage of capsules at 15–25°C. We hypothesized that there would be no difference in stability or pharmacokinetic parameters between freezer‐stored and room‐temperature Atopica® capsules. Animals Eight healthy research beagle dogs received one 5.0 mg/kg oral dose each of freezer‐stored and room‐temperature Atopica® capsules with a 1 week washout period between. Methods Ciclosporin concentrations of all available Atopica® capsule strengths were assessed for stability after −20°C storage at five time points over 30 days and at room temperature (15–25°C). A blinded, randomized cross‐over study was also performed to compare blood concentrations of ciclosporin after capsule storage for 28 days at −20 versus 15–25°C. Blood samples were obtained over a 24 h period after administration. Capsule and whole‐blood ciclosporin concentrations were assessed via high‐performance liquid chromatography–tandem mass spectrometry. Results There was no significant difference in stability between freezer‐stored and room‐temperature Atopica® capsules at any time point. In the cross‐over study, there were no significant differences in pharmacokinetic parameters assessed. Conclusions and clinical importance Placing Atopica® capsules in a −20°C freezer for 28 days does not affect stability or absorption in the dog. Résumé Contexte Placer les capsules de ciclosporine (Atopica_; Novartis Animal Health, Greensboro, NC, USA) dans un congélateur avant de l'administrer pourrait réduire l'incidence des vomissements chez le chien. Cependant on ne connait pas l'impact sur la stabilité et la pharmacocinétique de la ciclosporine. Hypothèses/Objectifs Le but de cette étude était d'évaluer la stabilité des capsules d'Atopica et la pharmacocinétique de la ciclosporine chez le chien après conservation à ‐20°C en comparaison avec un stockage des capsules entre 15 et 20°C. Nous supposons qu'il n'y aurait aucune différence de stabilité des paramètres pharmacocinétiques entre le stockage au congélateur et à température ambiante des capsules d'Atopica. Sujets Huit